Note re ALNY - most of their slide decks, posters etc, are protected PDF format so I cannot extract images to upload to the Alnylam research pages here at BiotechDueDiligence - so check the individual drug program sections for links to download the complete PDF files.

5/25/11 webcast: by this time in 2012 will have 5 programs in the clinic

5/25/11 webcast: expect to form additional partnerships in 2011

“5x15 strategy” - focus on genetically defined diseases, goal is to have 5 programs in late stage trials by the end of 2015. Intend to commercialize these drugs alone in the US and perhaps other countries, seek ROW partners. The first 3 of these programs have been identified as ALN-TTR01, ALN-PCS, and ALN-HPN (see details on each program below). The fourth and fifth drug candidates will be selected and announced from current internal programs by the end of 2011 (reiterated 5/2/11). Each of these programs would share the following attributes:

1. A genetically defined target and disease2. The potential to have a significant impact in high unmet need patient populations3. The ability to leverage our existing RNAi delivery platform4. The opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept5. The existence of clinically relevant endpoints for the filing of NDA with a focused patient database and possible accelerated paths for commercialization”

Other “partner-based programs” are also advancing as described below, as well as undisclosed early stage internal programs and a research alliance with Takeda (see below)

R&D expenses $106.4m in 2010, $108.7m in 2009, and $96.9m in 2008...2010 10k: expect losses over next several years at least"

5/2/11: R&D expense $26m in 1q2011, will decrease slightly the rest of the year

Manufacturing: "Under our agreements with Tekmira, we are obligated to utilize Tekmira for the manufacture of all LNP-formulated product candidates covered by Tekmira's intellectual property beginning during pre-clinical development and continuing through Phase II clinical trials. During 2009, we and Tekmira entered into a manufacturing and supply agreement under which we are committed to pay Tekmira a minimum of CAD$11.2 million (representing U.S.$9.2 million at the time of execution) through December 2011 for manufacturing services. Tekmira is currently manufacturing the clinical drug supply for our Phase I clinical trials of ALN-VSP and ALN-TTR01"

Antisense therapeutics: "Antisense technology uses short, single-stranded, DNA-like molecules to block mRNAs encoding specific proteins. An antisense oligonucleotide, or ASO, contains a sequence of bases complementary to a sequence within its target mRNA, enabling it to attach to the mRNA by base-pairing. The attachment of the ASO may lead to breakdown of the mRNA, or may physically block the mRNA from associating with the protein synthesis machinery of the cell. In either case, production of the protein encoded by the mRNA may be reduced. Typically, the backbone of an ASO, the linkages that hold its constituent bases together, will carry a number of chemical modifications that do not exist in naturally occurring DNA. These modifications are intended to improve the stability and pharmaceutical properties of the ASO. While we believe that RNAi drugs may potentially have significant advantages over ASOs, including greater potency and specificity, others are developing ASO drugs that are currently at a more advanced stage of development than RNAi drugs. For example, Isis has developed an ASO drug, Vitravene®, which is currently on the market, and has several ASO product candidates in clinical trials, including mipomersen, which is a lipid-lowering drug being developed by Isis in collaboration with Genzyme Corporation, or Genzyme. In addition, a number of other companies have product candidates in various stages of pre-clinical and clinical development. Included in these companies are Santaris, Genta Incorporated and AVI BioPharma, Inc. Because of their later stage of development, ASOs, rather than siRNAs, may become the preferred technology for drugs that target mRNAs in order to turn off the activity of specific genes."

Sources of Revenue (2010 10k)

Note: NVS and government revenue will cease after 2010, Roche and Takeda will remain steady"Other includes Regulus accounting flowthru, Cubist deal1q2011 revenue: $14.0m from Roche, $5.8m from Takeda, $1.1m other (via 3/31/11 10q)